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Bialellic Mutations in Tetratricopeptide Repeat Domain 7A (TTC7A) Cause Common Variable Immunodeficiency-Like Phenotype with Enteropathy

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Author information

Authors and Affiliations

  1. Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Wellcome Trust Brenner Building, St James’s University Hospital, Beckett Street, Leeds, UK

    Dylan Lawless, Mark Hull & Rashida Anwar

  2. Department of Clinical Immunology and Allergy, St James’s University Hospital, Beckett Street, Leeds, UK

    Anoop Mistry, Philip M. Wood, Gururaj Arumugakani, Clive Carter & Sinisa Savic

  3. Department of Pathology, St James’s University Hospital, Beckett Street, Leeds, UK

    Jens Stahlschmidt

  4. Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh, UK

    David Parry

  5. National Institute for Health Research—Leeds Musculoskeletal Biomedical Research Unit (NIHR-LMBRU) and Leeds Institute of Rheumatic and Musculoskeletal Medicine (LIRMM), Wellcome Trust Brenner Building, St James’s University Hospital, Beckett Street, Leeds, UK

    Sinisa Savic

  6. Department of Clinical Immunology and Allergy, National Institute for Health Research—Leeds Musculoskeletal Biomedical Research Unit (NIHR-LMBRU) and Leeds Institute of Rheumatic and Musculoskeletal Medicine (LIRMM), Wellcome Trust Brenner Building, St James University, Beckett Street, Leeds, LS9 7TF, UK

    Sinisa Savic

Authors
  1. Dylan Lawless
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  2. Anoop Mistry
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  3. Philip M. Wood
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  5. Gururaj Arumugakani
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  6. Mark Hull
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  8. Rashida Anwar
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  9. Clive Carter
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  10. Sinisa Savic
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Corresponding author

Correspondence to Sinisa Savic.

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The authors declare that they have no conflict of interest.

Additional information

Capsule Summary

TTC7A deficiency typically causes severe gastrointestinal manifestations such as multiple intestinal atresia or early-onset inflammatory bowel disease. In some cases, this is associated with severe combined immunodeficiency. Partial loss-of-function mutations appear to be associated with a milder phenotype resulting in common variable immunodeficiency-like condition with enteropathy.

Electronic supplementary material

Fig E1

Sanger sequence electropherogram of pedigree. Sanger sequence electropherogram of the proband II.ii for exon 16/20 c.1817 aAg/aGg (K606R) and exon 17/20 c.2014 Tct/Cct (S672P). Heterozygosity of A1817G paternally I.i and T2014C maternally I.ii. Healthy siblings II.i, II.iii and II.iv (arranged by age left to right on pedigree) show no presence of affected alleles. (GIF 71 kb)

High resolution image (TIFF 25622 kb)

Fig E2

Ribbon structure model of TTC7A and tetratricopeptide repeat domains. All known pathogenic variants in apoptotic enterocolitis, multiple intestinal atresias, combined immunodeficiency, and enteropathy-lymphocytopenia-alopecia are mapped. Annotation colors match that of the gene representation of Fig. 1 A. Protein changes, purple; stop codon, red; frame shift, green; exon skipping causing variants, orange; retained intron, blue. Tetratricopeptide repeat domains (TPR) are identified as cartoons also corresponding to horizontal bars shown in Fig. 1 A. Tetratricopeptide repeat domains (1–9) 121–157 and 177–210 Red, 414–447 orange, 497–531 yellow, 533–565 Green, 566–599 Cyan, 745–778 Blue, 780–812 Purple, 813–846 Magenta. (GIF 215 kb)

High resolution image (TIFF 6622 kb)

Fig E3

Modeling report. Detailed template report for data used with Phyre2 software indicating alignment, coverage, confidence and % i.d. Template Information 1–20 used for model construction. (PDF 858 kb)

Fig E4

Sequence structure report. Phyre2 software report of secondary structure and disorder prediction showing disorder confidence and conserved domain information. (PDF 172 kb)

Table E1

(DOCX 41 kb)

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Lawless, D., Mistry, A., Wood, P.M. et al. Bialellic Mutations in Tetratricopeptide Repeat Domain 7A (TTC7A) Cause Common Variable Immunodeficiency-Like Phenotype with Enteropathy. J Clin Immunol 37, 617–622 (2017). https://doi.org/10.1007/s10875-017-0427-1

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  • DOI: https://doi.org/10.1007/s10875-017-0427-1

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